Ultraviolet radiation in sunlight is the major cause of skin cancer in humans. However, individuals differ considerably in their susceptibility to cancer of the skin as well as cancer in other organs. The overall goal of this project is to understand the mechanisms involved in determining individual susceptibility to skin cancer. This goal will be addressed in a previously identified group of Maryland watermen who are at high risk for non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma). Accurate estimates of individual lifetime UV exposures have been calculated for each individual from a combination of interview data, working characteristics, and field and laboratory measurements. therefore, the major risk factor for skin cancer, UV exposure, can be easily controlled. Other phenotypic characteristics which influence risk for skin cancer such as skin pigmentation, ease of sunburning (skin type), and hair color, have been recorded for all individuals. This study will examine the role of DNA repair efficiency in susceptibility to non-melanoma skin cancer. DNA repair efficiency of cancer cases and matched controls will be assessed by two DNA repair assays: a lymphocyte- plasmid reactivation assay and an immunoassay for DNA photoproduct repair in lymphocytes and fibroblasts. Other variables such as lifetime UV exposure, sun sensitivity and skin type will be controlled for in the analyses. Association between age at onset of cancer and DNA repair efficiency will also be examined. The results of this study should i) contribute to our overall understanding of the mechanisms that determine susceptibility to skin cancer (and other cancers) in man, ii) aid in the identification of individuals at elevated risk for skin cancer, and iii) be useful in estimating increased risks to the general population resulting from potential increases in solar UV at the earth's surface.